Electrical stimulation of nerves has been in use for therapeutic purposes for more than 40 years.
For example Melzack and Wall 1965 described how analgesia could be produced when Aβ nerve fibres are stimulated at 100 Hz, a frequency that none of the other afferent fibres can follow faithfully. Wall 1986 produced these effects by applying the current through needles inserted into the patient's nerves. To avoid possible complications of inserting needles, he soon employed surface electrodes, leading to the term Transcutaneous Electrical Nerve Stimulation (TENS).
A typical TENS machine develops a pulse whose width can be varied from 50-250 μs, employing a current whose amplitude can be increased from 0-50 mA, and whose frequency is in the range of 1 to 250 Hz. The pulse width is sufficiently long in duration to excite Aβ fibres at low voltage causing a painless tingling and stimulation of interneurones releasing GABA. Johnson et al 1991 showed that ‘high intensity stimulation’, where the amplitude is increased sufficiently to recruit Aδ fibres, invokes release of met-enkephalin in the spinal cord which produces a more prolonged analgesic effect than that provided by the release of GABA produced by the more usual ‘low intensity stimulation’ of Aβ fibres. Salar et al 1981 observed that opioids were released slowly into the cerebrospinal fluid when TENS is performed at frequencies of 40-60 Hz and at amplitudes of 40-80 mA, signals that readily recruit Aδ fibres and whose firing is associated with sharp pain.
It is generally believed that TENS analgesia is caused mainly by cutaneous afferent fibre activation. However, Radkarishnan et al 2005 demonstrated that by differentially blocking cutaneous and deep tissue primary afferents, activation of large diameter primary afferents from deep somatic tissues, and not cutaneous afferent fibres, are pivotal in causing TENS analgesia.
A potential limitation of the effectiveness of TENS stimulation may therefore be that intensity of stimulation is limited by pain arising from activation of Aδ and C-fibres lying immediately under the electrodes.
As tissue impedance is capacitive, impedance tends to fall as frequency is increased. In order to increase tissue penetration, signals may be provided at a frequency where the intervals between each electric signal are less than the refractory periods of fibres that require stimulation. In order to produce action potentials, such signals are modulated to provide low frequency stimulation either by interference or interruption.
The interference method of applying medium frequency currents is exemplified by Nemec U.S. Pat. No. 2,622,601 “Electrical Nerve Stimulator”, Griffith U.S. Pat. No. 3,096,768 “Electrotherapy System” (Firmtron Inc) and many others. Two signal sources are each connected to a pair of electrodes. They can produce an amplitude modulated medium frequency signal in the tissues called interferential current, as follows. The first signal source uses a medium frequency carrier wave (typically 4.0 kHz) while the other operates at a slightly different frequency (typically 4.1 kHz). Their respective pairs of surface electrodes are arranged on the body in a manner that allows the two oscillating currents to intersect in deep tissues where interference is produced at a beat frequency in the low frequency range, typically at 100 Hz. This in turn is said to stimulate deeply placed Aβ fibres to produce analgesia.
However, there has been controversy as to whether or not a beat frequency is required to cause action potentials. Palmer et al 1999 discovered that when there is no interference frequency, i.e. the patient is receiving currents from both signal generators at 4 kHz and this frequency is no longer subjected to amplitude modulation, sensation still occurs. Moreover, the threshold of sensation generated in this way at 4 kHz takes place at lower amplitude than that produced by low frequency signals at less than 100 Hz. Signals administered at a frequency higher than any individual fibre can respond to on a 1:1 basis will produce asynchronous volleys in a nerve trunk as a result of action potentials arising in any axons in the vicinity of the next signal that by coincidence are no longer refractory.
Another method of improving tissue penetration in transcutaneous stimulation devices is described in Carter and Siff U.S. Pat. No. 7,130,696 “Percutaneous electrode array” in which the electrode is constructed from an array of microscopic pins that are intended to penetrate the outer layers of the skin thereby overcoming the electrical impedance of these layers.
Macdonald and Coates U.S. Pat. No. 5,776,170 “Electrotherapeutic apparatus” (1995) explored the effects of applying electric signals whose pulse width is so brief, typically 4 μs, that the voltage gated channels lying in excitable membranes of peripheral fibres that lie in the path of the current do not have time to respond to these signals sufficiently to reach membrane threshold and produce action potentials. This form of electrotherapy produces analgesic and mood altering effects provided that surface electrodes are placed over the spinal cord. Macdonald and Coates 1995 called this method TSE (Transcutaneous Spinal Electroanalgesia).
Littlewood et al GB2414410 “Electrotherapy Apparatus” (Bioinduction Ltd, 2005) discusses the effects of employing short high power electrotherapy waveforms for therapeutic purposes and describes the relationship between pulse width and the generation of action potentials and shows that the current in the tissues may be controlled independently of the level of sensation perceived by the patient.
Although the TENS method is reasonably well accepted by patients, it tends to produce a rather short-lived, localized region of pain relief. This is perhaps because of the aforementioned limitation on stimulation intensity caused by pain at the site of the electrodes and also because each electrode probably stimulates only those Aβ fibres that lie in the immediate vicinity of the electrodes. Accordingly, in patients where there is pain in several areas of the body, there is a need to improve the method, to produce a more long-lasting and generalized form of pain relief.
In 1967 in order to activate more Aβ fibres, electrodes were implanted by Professor Norman Shealy (Shealy et al 1967, 1971) in the spinal canal to stimulate the central nervous system, in particular the dorsal column (tracts through which the Aβ fibres pass up and down the spinal cord). Now termed Spinal Cord Stimulation (SCS), a repetitive low frequency pulse is employed typically at a frequency of 100 Hz or less and a pulse width in excess of 50 μs. When SCS is effective, a tingling sensation (paraesthesia) is perceived in the painful region of the body.
Since the invention of SCS by Shealy, many advances have been made in implanted devices for controlling chronic pain by means of electrical stimulation. The application of such devices has also been extended to include implanted deep brain stimulation, for pain relief and also to treat a range of conditions, for example Parkinson's disease.
Whereas transcutaneous stimulators tend to use only a few electrodes, often one or two pairs, implanted stimulators with four, eight or more pairs of electrodes are well known in the art. An early example, Timm and Bradley U.S. Pat. No. 3,646,940 “Implantable Electronic Stimulator Electrode and Method” (1969) described an apparatus for stimulation of muscles which includes a plurality of electrodes wherein a timed sequence of stimulating pulses is applied to the electrodes such that secondary tissue stimulation (that caused by current flowing between nearby electrode pairs) is eliminated.
For convenience, multiple electrode contacts are often combined on a single carrier and these arrays of electrodes are widely used today in spinal cord stimulators. For example, Borkan Savino and Waltz “Multi-electrode catheter assembly for spinal cord stimulation” U.S. Pat. No. 4,379,462 (Neuromed Inc, 1980) describes a linear array of four electrodes spaced in-line along the exterior of a catheter electrode assembly. An advantage of this type of electrode is that it is easy to insert in into the epidural space by means of a needle. These electrodes are referred to today by the term “Percutaneous electrode” because of the introduction method used.
Today percutaneous electrodes with eight contacts are often employed and two may be inserted into the epidural space, connected to a sixteen output stimulator. The surgeon programs different combinations of electrodes via wireless telemetry to stimulate a particular region of tissue in order to produce the desired therapeutic result. An array of electrodes also provides a degree of protection against migration, as it may be possible to reconfigure the electrode combination to compensate for small movements in the implanted array, to continue to stimulate a particular target area of tissue without a surgical procedure.
Another typical lead configuration is described in Hull Cross and Langley “Method of using a spinal cord stimulation lead” U.S. Pat. No. 5,417,719 (Medtronic Inc, 1993). This describes a type of “paddle electrode” so called because of the shape of the end of the lead which contains an array of electrodes located on the lead paddle. Each electrode is independently selectable such that the spinal cord may be stimulated as required.
Recent developments have attempted to increase the ability of the surgeon and/or patient to stimulate a particular area of tissue. Gord “Programmable current output stimulus stage for implantable device” U.S. Pat. No. 6,181,969 (Advanced Bionics Inc, 1999) describes a programmable output current source for use within an implantable stimulator, wherein for example sixteen individual current sources may be employed to control the flow of current in an array of electrodes. Woods et al “Implantable generator having current steering means” U.S. Pat. No. 6,909,917 (Advanced Bionics Inc, 2003) describes a means of determining a desired electrode stimulation pattern by way of a directional programming technique that translates the movement for instance of a joystick into current levels on an array of electrodes. An objective of this technique is to provide fine control over the region of tissue that is stimulated, beyond that provided by the physical locations of the individual electrodes. A disadvantage is the complexity of the stimulator device, having sixteen current controlled outputs, and the relatively poor efficiency at mid range current output which is typical of a linear electronic design, thereby compromising battery life of the implant.
There also exists in the prior art the use of pulse width modulation as a technique which has been applied across many power electronic applications in order to improve efficiency. For example MacDonald “Pulsewidth Electrical Stimulation” U.S. Pat. No. 7,054,686 (Biophan Technologies Inc, 2002) describes an apparatus that employs a series of individual pulses to improve efficiency in (for example) cardiac pacing.